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Synthesis of hollow ferrite nanospheres for biomedical applications
ARTICLE IN PRESS Journal of Magnetism and Magnetic Materials 321 (2009) 1414–1416
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
Synthesis of hollow ferrite nanospheres for biomedical applications Masaru Tada a,, Takashi Kanemaru a, Takeshi Hara a, Takashi Nakagawa a, Hiroshi Handa b, Masanori Abe a a b
Department of Physical Electronics, Tokyo Institute of Technology, Meguro-ku, 2-12-1, Ookayama, Meguro, Tokyo, 152-8552, Japan Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
a r t i c l e in f o
a b s t r a c t
Available online 20 February 2009
Hollow ferrite spheres of 220–340 nm diameter were synthesized at 60 1C as multi-functionalized magnetic carriers which are potentially applicable both as drug delivery systems (DDS) and hyperthermia treatment. We found that SH and OH groups on the silica template spheres enabled the fabrication of continuous ferrite shells of 20–30 nm in thickness. Transmission electron microscopy and energy-dispersive spectroscopy revealed that the templates were dissolved by a NaOH solution, yielding hollow particles exhibiting saturation magnetization of 78 emu/g. The results suggested that the ferrite shells are porous and the pores work as pathway for releasing drugs from the hollow particle inside. & 2009 Elsevier B.V. All rights reserved.
Keywords: Hollow sphere Spinel ferrite Drug delivery carrier Aqueous solution synthesis Ferrite plating
0. Introduction
1. Experiments
Recently, the fabrication and application of magnetic hollow spheres attracted attention, since the hollow structure is advantageous in holding drugs without further modification on the surface [1]. Hollow ferrite spheres are proposed to be used as heating agent for anti-cancer magnetic hyperthermia treatment [2], and thus they are potential candidate for multi-functionalized magnetic carriers which can work both as anti-cancer hyperthermia and drug delivery system. Caruso et al. synthesized hollow ferrite spheres by integrating SiO2 and Fe3O4 nanoparticles into anionic polystyrene as templates which were burned out by heat treatment at 500 1C [3]. Zhu et al. reported a template free solvothermal synthesis using ethylene glycol and FeCl3 at 200 1C [4]. Wu et al. reported low-temperature synthesis of magnetic hollow spheres introducing silica as a binder [5]. The purpose of this study is to synthesize self-standing hollow ferrite spheres from an aqueous solution at low temperature without the use of binders [5] or high temperatures to burn out the templates [3]. We attempted to fabricate a continuous ferrite layer onto commercially available silica (SiO2) spheres having different functional groups on their surfaces. The silica template was then dissolved in a NaOH solution and the morphology of the resultant particles investigated.
The silica spheres (180 nm in diameters) with OH groups on their surfaces were provided from Nissan Chemical Industries Ltd., and those with SH, NH2, and COOH (300, 200, and 200 nm in diameter, respectively) were purchased from Micromod Partikeltechnologie GmbH. A colloidal solution of respective silica spheres (5 mg) was mixed into a 40 ml reaction solution containing FeCl2 (10 mmol/l), CH3COONa (1 mol/l, a pH buffer), and NaNO3 (250 mmol/l, an oxidizing agent) at room temperature under bubbling N2 gas. The mixture was raised to 60 1C and kept for 3 h to deposit ferrite shell layers on the template surfaces by ferrite plating, an aqueous solution utilizing Fe2+-Fe3+ oxidation [6,7], under vigorous stirring and bubbling N2 gas. The resultant particles were separated with a magnet and washed with distilled water, which were subjected to a NaOH solution treatment (1 mol/l, 40 ml) at 60 1C for 3 h to dissolve the silica template. Crystal phase, saturation magnetization, chemical composition, and microstructures of prepared samples were investigated using X-ray diffraction (XRD), vibrating sample magnetometer (VSM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscope (TEM), respectively.
Corresponding author. Tel./fax: +81 3 5734 2394.
E-mail address: [email protected] (M. Tada). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.02.053
2. Results and discussion Fig. 1 shows that after ferrite plating, the OH- and SH-modified silica (SiO2) spheres were encapsulated in a continuous shell layer consisting of grains, 20–30 nm in size, which coincides with the layer thickness. On the other hand, the shell layer was not formed on the silica spheres with NH2 or COOH groups. This means that
ARTICLE IN PRESS M. Tada et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1414–1416
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Fig. 3. EDX spectra observed for ferrite-plated silica particles (a) and the particles after a NaOH solution treatment to ferrite-plated silica particles (b).
Fig. 1. TEM images of core–shell particles after ferrite plating on (a) OH-modified silica spheres of 180 nm size, and (b) SH-modified silica spheres sized 300 nm.
Fig. 2. Representative XRD pattern observed for ferrite-plated silica spheres modified with SH groups.
COOH or NH2 on the silica surface in this case did not work as ferrite growth site, though amino acids are abundantly conjugated onto ferrite surface intermediated by COOH groups [8]. The XRD analysis (Fig. 2) on the ferrite-plated SH-modified silica spheres revealed that all the reflection peaks are assigned to cubic spinel and no impurity phase is detected. All the samples exhibited similar patterns within experimental accuracy. Also, the crystal-
Fig. 4. TEM images of hollow ferrite spheres synthesized by using (a) OH-modified silica templates sized 180 nm and (b) SH-modified silica templates of 300 nm.
line phase of the samples did not change even after the treatment with a NaOH solution. Fig. 3 shows that Si Ka peak at 1.7 keV observed for core–shell particles (Fig. 3a) disappeared after the treatment with a NaOH solution (Fig. 3b), and therefore the resultant particles are completely free from SiO2. As shown in Fig. 4, the ferrite shells maintained their structure after the templates were removed, and the obtained hollow sphere consist
ARTICLE IN PRESS 1416
M. Tada et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1414–1416
solution at the low temperature of 60 1C with the help of a silica spherical template having OH and SH groups on their surfaces. We found that SH groups on the silica spherical template facilitated synthesis of ferrite layers with neighboring grains fused to each other, which enabled the formation of self-standing hollow ferrite spheres in good yield. Our hollow ferrite nanospheres were prepared without using high temperature (to fuse grains and/or burn out the template [3,4]) and binders [5], which has, to our knowledge, not been done before and is advantageous. With their porous shells, the hollow ferrite nanospheres synthesized in this study are potentially applicable as multi-functionalized carriers both for drug delivery systems (DDS) and magnetic hyperthermia, and maybe even in combination of both. Fig. 5. Magnetization curve for hollow ferrite spheres synthesized in this study.
of porous ferrite shell whose pores worked as pathway to transfer the dissolved SiO2 away from inside. The magnetization curve (Fig. 5) showed that the hollow ferrite spheres had saturation magnetization of 78 emu/g, a value expected for an intermediate between g-Fe2O3 and Fe3O4. Furthermore, the hollow nanospheres were obtained in better yield when the SH-modified silica spheres were introduced as template (Fig. 4a) than when OH-modified spheres were used (Fig. 4b). This suggests that the SH groups facilitated ferrite layer growth as compared to the OH groups. The obtained hollow ferrite spheres consist only of ferrite shell, of which neighboring ferrite grains strongly bonded to each other.
3. Conclusions In conclusion, the hollow ferrite nanospheres consist of porous ferrite shells and were successfully synthesized from an aqueous
Acknowledgement The EDX measurements was technically supported by Mr. Y. Watanabe, Center for Advanced Materials Analysis, Tokyo Institute of Technology. References [1] F. Caruso, Chem. Eur. J. 6 (2003) 413. [2] M. Kawashita, K. Sadaoka, T. Kokubo, et al., J. Mater. Sci. Mater. Med. 17 (2006) 605. [3] F. Caruso, M. Spasova, A. Susha, et al., Chem. Mater. 13 (2001) 109. [4] L.-P. Zhu, H.-M. Xiao, W.-D. Zhang, et al., Cryst. Growth Des. 8 (2008) 957. [5] W. Wu, D. Caruntu, A. Martin, et al., J. Magn. Magn. Mater. 311 (2007) 578. [6] M. Abe, Y. Tanno, Y. Tamaura, J. Appl. Phys. 57 (1985) 3795. [7] M. Abe, Y. Kitamoto, K. Matsumoto, et al., IEEE Trans. Magn. 33 (1997) 3649. [8] K. Nishio, N. Gokon, et al., Colloid Surf. B-Biointerfaces 54 (2007) 249.
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
Synthesis of hollow ferrite nanospheres for biomedical applications Masaru Tada a,, Takashi Kanemaru a, Takeshi Hara a, Takashi Nakagawa a, Hiroshi Handa b, Masanori Abe a a b
Department of Physical Electronics, Tokyo Institute of Technology, Meguro-ku, 2-12-1, Ookayama, Meguro, Tokyo, 152-8552, Japan Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan
a r t i c l e in f o
a b s t r a c t
Available online 20 February 2009
Hollow ferrite spheres of 220–340 nm diameter were synthesized at 60 1C as multi-functionalized magnetic carriers which are potentially applicable both as drug delivery systems (DDS) and hyperthermia treatment. We found that SH and OH groups on the silica template spheres enabled the fabrication of continuous ferrite shells of 20–30 nm in thickness. Transmission electron microscopy and energy-dispersive spectroscopy revealed that the templates were dissolved by a NaOH solution, yielding hollow particles exhibiting saturation magnetization of 78 emu/g. The results suggested that the ferrite shells are porous and the pores work as pathway for releasing drugs from the hollow particle inside. & 2009 Elsevier B.V. All rights reserved.
Keywords: Hollow sphere Spinel ferrite Drug delivery carrier Aqueous solution synthesis Ferrite plating
0. Introduction
1. Experiments
Recently, the fabrication and application of magnetic hollow spheres attracted attention, since the hollow structure is advantageous in holding drugs without further modification on the surface [1]. Hollow ferrite spheres are proposed to be used as heating agent for anti-cancer magnetic hyperthermia treatment [2], and thus they are potential candidate for multi-functionalized magnetic carriers which can work both as anti-cancer hyperthermia and drug delivery system. Caruso et al. synthesized hollow ferrite spheres by integrating SiO2 and Fe3O4 nanoparticles into anionic polystyrene as templates which were burned out by heat treatment at 500 1C [3]. Zhu et al. reported a template free solvothermal synthesis using ethylene glycol and FeCl3 at 200 1C [4]. Wu et al. reported low-temperature synthesis of magnetic hollow spheres introducing silica as a binder [5]. The purpose of this study is to synthesize self-standing hollow ferrite spheres from an aqueous solution at low temperature without the use of binders [5] or high temperatures to burn out the templates [3]. We attempted to fabricate a continuous ferrite layer onto commercially available silica (SiO2) spheres having different functional groups on their surfaces. The silica template was then dissolved in a NaOH solution and the morphology of the resultant particles investigated.
The silica spheres (180 nm in diameters) with OH groups on their surfaces were provided from Nissan Chemical Industries Ltd., and those with SH, NH2, and COOH (300, 200, and 200 nm in diameter, respectively) were purchased from Micromod Partikeltechnologie GmbH. A colloidal solution of respective silica spheres (5 mg) was mixed into a 40 ml reaction solution containing FeCl2 (10 mmol/l), CH3COONa (1 mol/l, a pH buffer), and NaNO3 (250 mmol/l, an oxidizing agent) at room temperature under bubbling N2 gas. The mixture was raised to 60 1C and kept for 3 h to deposit ferrite shell layers on the template surfaces by ferrite plating, an aqueous solution utilizing Fe2+-Fe3+ oxidation [6,7], under vigorous stirring and bubbling N2 gas. The resultant particles were separated with a magnet and washed with distilled water, which were subjected to a NaOH solution treatment (1 mol/l, 40 ml) at 60 1C for 3 h to dissolve the silica template. Crystal phase, saturation magnetization, chemical composition, and microstructures of prepared samples were investigated using X-ray diffraction (XRD), vibrating sample magnetometer (VSM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscope (TEM), respectively.
Corresponding author. Tel./fax: +81 3 5734 2394.
E-mail address: [email protected] (M. Tada). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.02.053
2. Results and discussion Fig. 1 shows that after ferrite plating, the OH- and SH-modified silica (SiO2) spheres were encapsulated in a continuous shell layer consisting of grains, 20–30 nm in size, which coincides with the layer thickness. On the other hand, the shell layer was not formed on the silica spheres with NH2 or COOH groups. This means that
ARTICLE IN PRESS M. Tada et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1414–1416
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Fig. 3. EDX spectra observed for ferrite-plated silica particles (a) and the particles after a NaOH solution treatment to ferrite-plated silica particles (b).
Fig. 1. TEM images of core–shell particles after ferrite plating on (a) OH-modified silica spheres of 180 nm size, and (b) SH-modified silica spheres sized 300 nm.
Fig. 2. Representative XRD pattern observed for ferrite-plated silica spheres modified with SH groups.
COOH or NH2 on the silica surface in this case did not work as ferrite growth site, though amino acids are abundantly conjugated onto ferrite surface intermediated by COOH groups [8]. The XRD analysis (Fig. 2) on the ferrite-plated SH-modified silica spheres revealed that all the reflection peaks are assigned to cubic spinel and no impurity phase is detected. All the samples exhibited similar patterns within experimental accuracy. Also, the crystal-
Fig. 4. TEM images of hollow ferrite spheres synthesized by using (a) OH-modified silica templates sized 180 nm and (b) SH-modified silica templates of 300 nm.
line phase of the samples did not change even after the treatment with a NaOH solution. Fig. 3 shows that Si Ka peak at 1.7 keV observed for core–shell particles (Fig. 3a) disappeared after the treatment with a NaOH solution (Fig. 3b), and therefore the resultant particles are completely free from SiO2. As shown in Fig. 4, the ferrite shells maintained their structure after the templates were removed, and the obtained hollow sphere consist
ARTICLE IN PRESS 1416
M. Tada et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 1414–1416
solution at the low temperature of 60 1C with the help of a silica spherical template having OH and SH groups on their surfaces. We found that SH groups on the silica spherical template facilitated synthesis of ferrite layers with neighboring grains fused to each other, which enabled the formation of self-standing hollow ferrite spheres in good yield. Our hollow ferrite nanospheres were prepared without using high temperature (to fuse grains and/or burn out the template [3,4]) and binders [5], which has, to our knowledge, not been done before and is advantageous. With their porous shells, the hollow ferrite nanospheres synthesized in this study are potentially applicable as multi-functionalized carriers both for drug delivery systems (DDS) and magnetic hyperthermia, and maybe even in combination of both. Fig. 5. Magnetization curve for hollow ferrite spheres synthesized in this study.
of porous ferrite shell whose pores worked as pathway to transfer the dissolved SiO2 away from inside. The magnetization curve (Fig. 5) showed that the hollow ferrite spheres had saturation magnetization of 78 emu/g, a value expected for an intermediate between g-Fe2O3 and Fe3O4. Furthermore, the hollow nanospheres were obtained in better yield when the SH-modified silica spheres were introduced as template (Fig. 4a) than when OH-modified spheres were used (Fig. 4b). This suggests that the SH groups facilitated ferrite layer growth as compared to the OH groups. The obtained hollow ferrite spheres consist only of ferrite shell, of which neighboring ferrite grains strongly bonded to each other.
3. Conclusions In conclusion, the hollow ferrite nanospheres consist of porous ferrite shells and were successfully synthesized from an aqueous
Acknowledgement The EDX measurements was technically supported by Mr. Y. Watanabe, Center for Advanced Materials Analysis, Tokyo Institute of Technology. References [1] F. Caruso, Chem. Eur. J. 6 (2003) 413. [2] M. Kawashita, K. Sadaoka, T. Kokubo, et al., J. Mater. Sci. Mater. Med. 17 (2006) 605. [3] F. Caruso, M. Spasova, A. Susha, et al., Chem. Mater. 13 (2001) 109. [4] L.-P. Zhu, H.-M. Xiao, W.-D. Zhang, et al., Cryst. Growth Des. 8 (2008) 957. [5] W. Wu, D. Caruntu, A. Martin, et al., J. Magn. Magn. Mater. 311 (2007) 578. [6] M. Abe, Y. Tanno, Y. Tamaura, J. Appl. Phys. 57 (1985) 3795. [7] M. Abe, Y. Kitamoto, K. Matsumoto, et al., IEEE Trans. Magn. 33 (1997) 3649. [8] K. Nishio, N. Gokon, et al., Colloid Surf. B-Biointerfaces 54 (2007) 249.